Identification of biomarkers for metastatic osteosarcoma based on DNA microarray data

Abstract

Osteosarcoma (OS) is a malignant bone tumor very often with pulmonary metastasis and is the main cause of OS mortality. The objective of this study was to screen for possible biomarkers of metastatic OS to explore the mechanisms of pulmonary metastasis of OS through network construction. GSE14359 was downloaded from the Gene Expression Omnibus database, which included 5 samples from conventional OS group with 2 replicates and 4 samples from OS pulmonary metastasis group in duplicate. Differentially expressed genes (DEGs) between two groups were identified by limma packages in R and classical t-test with the threshold of the false discovery rate (FDR) <0.05. The Database for Annotation, Visualization and Integrated Discovery (DAVID) were then used to perform functional annotation (FDR < 0.01). Differential coexpression network was constructed with subspace differential coexpression analysis (SDC), and genes with high degrees in the differential coexpression network were identified.A total of 1344 genes were screened as DEGs, including 677 up-and 667 down-regulated DEGs in the pulmonary metastasis of OS. Thirty-one significantly enriched functions were obtained, such as blood vessel morphogenesis, defense response, cell death and so on. DEGs with high degrees (brain-specific angiogenesis inhibitor 2 (BAI2), formin-like 1 (FMNL1), dualspecificity phosphatase 7 (DUSP7), transient receptor potential melastatin 2 (TRPM2), CBP80/20-dependent translation initiation factor (KIAA0427) and C120rf35) in the differential coexpression network were found. BAI2, FMNL1, DUSP7 and TRPM2 may be useful markers for predicting tumor metastasis and therapeutic targets for the treatment of OS patients with metastasis. Key words: osteosarcoma, differentially expressed genes, differential coexpression network, gene ontologyOsteosarcoma (OS) is the most common primary malignant cancer of the bone in both children and young adults [1]. Moreover, approximately 15-20% of patients present with discernable metastasis [2], frequently for lung [3]. Though the overall recurrent-free survival rate over 5 years remains approximately 65% with neoadjuvant chemotherapy combined with surgery, while when pulmonary metastasis, less than 30% [4]. In addition, neoadjuvant chemotherapy remains controversial in the world [5]. The treatment for OS is very challenging. Hence, it is important to identify molecular targets to prevent pulmonary metastases during the early stage, and further to improve the prognosis of OS patients.The underlying pathogenesis has been difficult to establish because of its heterogeneous histology and complex etiology. Extensive efforts have been made to explore the potential etiology and molecular mechanisms. Reversion-inducing cysteine rich protein with Kazal motifs (RECK), a member of antiangiogenic factors, is down-regulated in OS [6]. The expression level of TGF-β1 is significantly higher in high-grade OS than low-grade OS [7]. Densmore et al. have shown that p53 can effectively reduce the number and the size of lung metastases ...

Adhesion GPCRs in Tumorigenesis

“…Unlike BAI1, the expression of BAI2 or BAI3 is not silenced in glioma cells [72]. Moreover, recent studies determined higher BAI2 expression in tumor metastasis and advanced stages [134, 135]. …”

Resistin enhances angiogenesis in osteosarcoma via the MAPK signaling pathway

“…Angiogenesis is key to the development of osteosarcoma, its subsequent progression and metastasis [3, 4]. Results from using differential co-expression network, finding angiogenesis is closely related to osteosarcoma progression and metastasis [5]. Thus, antiangiogenic therapy might be feasible for osteosarcoma patients [6].…”

Prediction of optimal gene functions for osteosarcoma using gene ontology and microarray profiles

“…For example, previous studies have implicated that high recurrence rate and metastatic potential of OS are connected with high levels of angiogenesis [36], [37]. Moreover, Wang et al [38] have used differential co-expression network to find that angiogenesis is closely related to OS progression and metastasis. Most importantly, suppression of cancer angiogenesis has been regarded as an attractive strategy for tumor therapy [39].…”